Reduced oxygen uptake efficiency slope in patients with cardiac sarcoidosis.

The non-invasive diagnosis of cardiac sarcoidosis (CS) is difficult. Cardiovascular magnetic resonance (CMR) has become a very valuable diagnostic tool in patients with suspected CS, but usually a combination of different tests is used. Oxygen uptake efficiency slope (OUES) is a parameter of cardiopulmonary exercise testing (CPET), which is used as an indicator for cardiovascular impairment. We investigated the predictive value of OUES for the diagnosis of myocardial involvement in sarcoid patients.Retrospectively 37 consecutive patients (44.9±13.8 years) with histologically confirmed sarcoidosis and clinical suspicion of heart involvement underwent noninvasive diagnostic testing including CMR. CS was diagnosed according to the guidelines from the Japanese Society of Sarcoidosis and other Granulomatous Disorders with additional consideration of CMR findings. Furthermore, CPET with calculation of predicted OUES according to equations by Hollenberg et al. was carried out.Patients with CS (11/37; 30%) had a worse cardiovascular response to exercise. OUES was significantly lower in CS-group compared to non-CS-group (59.3±19.1 vs 88.0±15.4%pred., p<0.0001). ROC curve method identified 70%pred. as the OUES cut-off point, which maximized sensitivity and specificity for detection of CS (96% sensitivity, 82% specificity, 89% overall accuracy). OUES <70%pred. was the single best predictor of CS (Odds ratio: 100.43, 95% CI: 1.99 to 5064, p<0.001) even in multivariate analyses.OUES assessed in CPET may be helpful in identifying patient with cardiac involvement of sarcoidosis. Patient selection for CMR may be assisted by CPET findings in patients with sarcoidosis

Eleven patients with evidence for Cardiac Sarcoidosis (CS).

<p>CMR  =  Cardiovascular Magnetic Resonance; EGE  =  Early myocardial Gadolinium Enhancement; LGE  =  Late myocardial Gadolinium Enhancement; LVEF  =  Left Ventricular Ejection Fraction; ECG  =  Electrocardiogram; OUES  =  oxygen uptake efficiency slope; RBBB  =  right bundle branch block; LBBB  =  left bundle branch block; PVC  =  premature ventricular contraction.</p><p>*Coronary angiography excluded significant obstructive coronary artery disease.</p>†<p>no CMR because of implanted pacemaker.</p

Summary of the 2006 revised guidelines of diagnosing cardiac sarcoidosis of the Japanese Society of Sarcoidosis and Other Granulomatous [7].

<p>RBBB  =  complete right bundle branch block. VT  =  ventricular tachycardia. PVC  =  premature ventricular contraction.</p

Association between observed and predicted cardiac sarcoidosis according to the best OUES cut-off point at 70% of predicted.

<p>Association between observed and predicted cardiac sarcoidosis according to the best OUES cut-off point at 70% of predicted.</p

Comparison of CPET parameters in patients with and without cardiac sarcoidosis (CS).

<p>Peak VO₂ [ml/min/kg] upper left, peak VO₂ [% of predicted] upper right, OUES [ml/min/log(ml/min)] lower left, and OUES (% of predicted) lower right panel. All panels: Outliers (values that are between 1.5 and 3 times the interquartile range) are represented by circles beyond the whiskers. Extreme values (values that are more than 3 times the interquartile range) are represented by asterisk beyond the whiskers. P-values are given for the univariable comparison.</p

Results of the multivariable analyses (stepwise forward p_in<0.05; p_out>0.1).

<p>Two models were calculated with either OUES in continuous (upper table) or as categorical values (70% predicted, lower table).</p

Summary of Demographic, CMR-, Pulmonary function tests and CPET-Data (n = 37).

<p>BMI  =  body mass index; BSA  =  body surface area; CMR  =  cardiovascular magnetic resonance; LVEF  =  left ventricular ejection fraction; CPET  =  cardiopulmonary exercise testing; EGE  =  Early gadolinium enhancement; LGE  =  Late gadolinium enhancement.</p><p>*Reference values according to equations published by Cooper et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0102333#pone.0102333-Cooper1" target="_blank">[21]</a></p>†<p>Reference values according to equations published by Hollenberg et al <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0102333#pone.0102333-Hollenberg1" target="_blank">[22]</a>.</p>‡<p>Wilcoxon signed-rang-test.</p>§<p>Unpaired Student's t-test.</p

The Receiver Operating Characteristic (ROC) curve of different OUES cut-off points (%pred) and CS diagnosis.

<p>A OUES <70% of predicted as cut-off point had the largest diagnostic discriminatory power for diagnosing cardiac sarcoidosis.</p